Pathology is the gold standard to discern diseases in humans and is essential to every discipline in the medical field. Human otopathology, because of difficulties and expense of acquisition and preparation of human temporal bones (HTBs), has evolved as a research discipline, and few laboratories in the USA are active in acquiring, preparing, and studying HTBs. By studying HTBs at various stages of disease using modern techniques, we can gain unique insight into the pathogenesis of each disease, rather than only the pathology, and therefore provide better clinical treatment. Studies on underlying ear pathologies and disease mechanisms heavily depend on postmortem HTBs, where the middle and inner ear structures can be closely examined. Our laboratory has collected 2,075 HTBs representing a variety of diseases, including 600+ specimens of otitis media, 16 different types of congenital genetic disorders consisting of more than 60 HTBs, and 42 HTBs with Meniere's disease which have been extensively used for the training and education of residents, and international clinicians and researchers. The laboratory has substantially contributed to the understanding of otitis media, genetic ear problems, otosclerosis, Meniere's disease, and other otological diseases with over 300 publications. The long-term objective of this proposal is to increase HTB research relevant to new discoveries in genetics, physiology, and disease by collaborating with the other active otopathology laboratories and the Registry, and to share HTB tissues by creating a collaborative infrastructure for research on human ear disorders to maximize impact and novelty while avoiding duplicative efforts. The following Specific Aims will be performed to accomplish our objective: 1) To investigate the pathogenesis of otitis media using human temporal bones;2) To study HTBs with congenital syndromic ear anomalies;3) To investigate pathology and pathogenesis of Meniere's disease using HTBs;4) To image HTBs using a novel, non-invasive method of thin-sheet laser imaging microscopy (TSLIM);5) To collaborate with the Otopathology Research Collaboration Network;6) To provide training of new otopathologists to modernize the field of human otopathology. PUBLIC HEALTH RELEVANCE: These studies will use innovative approaches to determine the pathogenesis of important otologic problems including otitis media, congenital sensorineural hearing loss, and Meniere's disease. Understanding the pathogenesis of the various diseases may have an important positive impact on facilitating the development of new strategies for prevention and treatment of the diseases and their complications.